Signaling mechanisms of egg activation

In a recent manuscript (PMID: 29183978) published in PNAS, Marc Kirschner and colleagues uncover characterize the changes in phosphorylation evoked by activation in the eggs of the African clawed frog, Xenopus leavis. Using mass spectrometry-based proteomics, this group demonstrates that egg activation results changes the phosphorylation state of several egg proteins, many of them with a half time of ~10 minutes.

One particularly intriguing finding is the convincing, albeit surprising, documentation that very few proteins change concentration with egg activation. Specifically, activation was accompanied by a reduction of the concentration of only 40 proteins (out of the more than 8,600 proteins quantified), and only 8 proteins increased in concentration. By contrast, 8,593 proteins had a stable concentration before and up to twenty minutes following egg activation.

Another intriguing finding to come out of this study are the proteins released within minutes of egg activation, presumably as part of the cotrical granule exocytosis. Various enzymes such as ovastacin and ovochymase were found to decrease in abundance in the egg, but were quantified in the collected from the media following egg activation. Surprisingly, protease inhibitors were also found to be released minutes after egg activation. Whereas the role that these protease inhibitors may play in fertilization, one potential role is to suppress ovastacin and ovochymase activity in the cortical granules.

Egg activation alters the phosphorylation status of many proteins, several of them playing predictable roles in the resumption of meiosis. Others were a bit more surprising. For example, approximately 25% of phosphate groups added with egg activation include the minimal consensus sequence for CaMKII. These data suggest a prominent role for this Ca2+-activated kinase with egg activation. Moreover, this kinase may play an important role in signaling of the slow block to polyspermy.

In sum, a careful examination of changes in the phosphoproteome during activation of X. laevis eggs has provided numerous insights into the proteins that signal the earliest stages of embryonic development.